Copyright © 2009 Pearson Education, Inc. Chapter 13 & 14 Essentials of Genetics Relationship between Gene Mutations, Amino Acid Side Chains, and Protein

Copyright © 2009 Pearson Education, Inc.

Chapter 13 & 14

Essentials of Genetics

Relationship between Gene Mutations, Amino Acid Side Chains, and Protein Structure


13.8: Chemical Nature of R-Groups

Each Side Chain has a characteristic chemical behavior. This behavior will determine the Secondary and Tertiary structure of a folded protein.


Predictable Behavior of Side Chains

Hydrophobic – R-groups will force the protein to fold and allow this side chain to be away from water.

Hydrophilic – R-groups want to be toward water.

Acids – R-groups will form ionic bonds with R-groups that are Bases.

The 3-D structure is a PRODUCT of the primary order of amino acids.


Protein Structure, a Reminder…Primary – straight chain of amino acids held together by peptide bonds.

Secondary – alpha helix or beta-pleated sheet held together by hydrogen bonds.

Tertiary – globular structure; 3-dimensional shape determined by side chain chemistry of individual amino acids.

Quarternary – more than one tertiary structures that fit together in a complimentary way.


How Does a Polypeptide Become a Protein?

• Folding occurs in the watery cytosol

• HydroPHOBIC amino acids want to be• Near other hydrophobic amino acids

• Away from the watery cytosol/in the interior of the folded structure.

• HydroPHILIC amino acids are located along the surface/outer edge

• Disulfide bonds form between cysteine molecules.

• Acids and bases form ionic bonds.


The Role of Chaperones• Chaperones are proteins that assist in the

folding of other proteins.

• Mediate the process of folding my preventing the formation of incorrect patterns.

• They do not become a part of the final product although they do bind to the polypeptide as it is folding.

• If the correct structure is NOT made UBIQUITINS tag them for destruction by proteasomes.


Impact of Mis-folding• Mis-folded proteins can be nonfunctional

• Sickle Cell Anemia

• EB

• OI

• Cystic fibrosis

• Mis-folded proteins can accumulate and cause cell destruction.

• Prion Diseases

• Huntington Disease

• Alzheimer Disease

• Parkinson Disease


13.9: Proteins Have Diverse Roles

• Proteins are the essence of cellular function.

• Most abundant organic macromolecule in cells.

• Structural/Fibrous proteins like collagen and keratin

• Contractile proteins like actin and myosin

• Functional/Globular proteins like hemoglobin, myoglobin, and immunoglobulins

• Largest functional group - Enzymes – biological catalysts that require a specifically shaped ACTIVE SITE for normal function.


14.1 Mutations Are Classified in Various Ways

• Mutation is any base pair change. • Can involve a single base pair substitution, deletion

or insertion of one or more bases, or major alterations in chromosome structure.

• How they occur: Spontaneous or Induced?• Where have they occurred/location?

• Somatic

• Germline• Autosomal• X-linked


14.1 Spontaneous or Induced

• Spontaneous mutations appear to have no known cause.

• No known agents are associated with this occurrence.• Assumed to be accidental.

• Induced mutations are due to an extraneous factor that may be natural or artificial.

• Examples include radiation and both natural and man-made chemicals.

• We call these MUTAGENS


14.1 Location

• Somatic occur in any cell except gametes• Mutations DO NOT pass on to offspring

• Germline occur in gametes• Mutations DO pass on to offspring

• Autosomal occur on autosomes• X-linked occur on X chromosomes

• Express differently in males and females due to presence of 1 or 2 X chromosomes.

Description of mutation can be combination of above terms:•Autosomal somatic•Autosomal germline•X-linked somatic•X-linked germline


Classification Based on Type of Molecular Change

If the triplet code does not


Point Mutation•Change in ONE nucleotide of a triplet•Occurs in protein-coding (exon) portion•Creates NEW triplet code•Same amino acid = silent mutation (degeneracy)•Different amino acid = missense mutation

• Same side chain group has less impact than different side chain group.

•Results in STOP codon = nonsense mutation

Frameshift Mutation•Alters reading frame, changes every amino acid following insertion or deletion.


What is their Phenotype effect?• Loss-of-function• Gain-of-function• Morphological• Nutritional• Behavioral• Lethal• Conditional


• Loss-of-function – reduces or eliminates function of gene.

• Null mutation – complete loss of function.• Gain-of-function – enhanced or new function.• Morphological – visible alterations of phenotype.• Nutritional – loss of ability to synthesize an amino

acid or vitamin.• Behavioral – difficult to analyze; defect that

changes mating behaviors, etc.• Lethal – interrupts process essential to survival.• Conditional – expression depends on

environment.

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Copyright © 2009 Pearson Education, Inc. Chapter 13 & 14 Essentials of Genetics Relationship between Gene Mutations, Amino Acid Side Chains, and Protein